Exercise-Induced Asthma Symptoms and Nighttime Asthma: Are They Similar to AHR?

Background. Asthma experienced during exercise and during the night is based on the presence of airway hyperresponsiveness (AHR). The aim of the present study was to examine whether AHR is a predictor of exercise-induced asthma (EIA) and nighttime symptoms. Material. We included 793 asthmatics subjects with symptoms and a positive asthma test. Results. Mean (SD) FEV1 was 93% (15), 71% had rhinitis, and 62% had atopy. Both EIA and nighttime symptoms were associated with AHR; however, when including other factors of importance in a multivariate analysis, logRDR was eliminated, whereas FEV1% pred (P < .001), smoking (P < .05), atopy (P < .001), sex (P < .001), and treatment (P < .01) were associated with having EIA while dyspnoea (P < .001), cough (P < .001), and eosinophils (P < .01) were associated with frequent night symptoms. The risk of having nighttime awakenings due to asthma was more than twofold higher among those with EIA symptoms than among those without symptoms (OR (CI95%) 2.77 (2.0–3.8) (P < .001)). In Conclusion. EIA and night symptoms are associated with AHR, but other factors of importance eliminated this close association. Night asthma is more closely associated with airway inflammation than AHR

SLT-VEGF Reduces Lung Metastases, Decreases Tumor Recurrence, and Improves Survival in an Orthotopic Melanoma Model

SLT-VEGF is a recombinant cytotoxin comprised of Shiga-like toxin (SLT) subunit A fused to human vascular endothelial growth factor (VEGF). It is highly cytotoxic to tumor endothelial cells overexpressing VEGF receptor-2 (VEGFR-2/KDR/Flk1) and inhibits the growth of primary tumors in subcutaneous models of breast and prostate cancer and inhibits metastatic dissemination in orthotopic models of pancreatic cancer. We examined the efficacy of SLT-VEGF in limiting tumor growth and metastasis in an orthotopic melanoma model, using NCR athymic nude mice inoculated with highly metastatic Line IV Cl 1 cultured human melanoma cells. Twice weekly injections of SLT-VEGF were started when tumors became palpable at one week after intradermal injection of 1 × 106 cells/mouse. Despite selective depletion of VEGFR-2 overexpressing endothelial cells from the tumor vasculature, SLT-VEGF treatment did not affect tumor growth. However, after primary tumors were removed, continued SLT-VEGF treatment led to fewer tumor recurrences (p = 0.007), reduced the incidence of lung metastasis (p = 0.038), and improved survival (p = 0.002). These results suggest that SLT-VEGF is effective at the very early stages of tumor development, when selective killing of VEGFR-2 overexpressing endothelial cells can still prevent further progression. We hypothesize that SLT-VEGF could be a promising adjuvant therapy to inhibit or prevent outgrowth of metastatic foci after excision of aggressive primary melanoma lesions

Green Bank Telescope Observations of the Eclipse of Pulsar "A" in the Double Pulsar Binary PSR J0737-3039

We report on the first Green Bank Telescope observations at 427, 820 and 1400 MHz of the newly discovered, highly inclined and relativistic double pulsar binary. We focus on the brief eclipse of PSR J0737-3039A, the faster pulsar, when it passes behind PSR J0737-3039B. We measure a frequency-averaged eclipse duration of 26.6 +/- 0.6 s, or 0.00301 +/- 0.00008 in orbital phase. The eclipse duration is found to be significantly dependent on radio frequency, with eclipses longer at lower frequencies. Specifically, eclipse duration is well fit by a linear function having slope (-4.52 +/- 0.03) x 10^{-7} orbits/MHz. We also detect significant asymmetry in the eclipse. Eclipse ingress takes 3.51 +/- 0.99 times longer than egress, independent of radio frequency. Additionally, the eclipse lasts (40 +/- 7) x 10^{-5} in orbital phase longer after conjunction, also independent of frequency. We detect significant emission from the pulsar on short time scales during eclipse in some orbits. We discuss these results in the context of a model in which the eclipsing material is a shock-heated plasma layer within the slower PSR J0737-3039B's light cylinder, where the relativistic pressure of the faster pulsar's wind confines the magnetosphere of the slower pulsar.Comment: 12 pages, 3 figure

Targeted scVEGF/(177)Lu radiopharmaceutical inhibits growth of metastases and can be effectively combined with chemotherapy

BACKGROUND: scVEGF/(177)Lu is a novel radiopharmaceutical targeted by recombinant single-chain (sc) derivative of vascular endothelial growth factor (VEGF) that binds to and is internalized by vascular endothelial growth factor receptors (VEGFR). scVEGF/(177)Lu potential as adjuvant and neoadjuvant anti-angiogenic therapy was assessed in metastatic and orthotopic mouse models of triple-negative breast cancer. METHODS: Metastatic lesions in Balb/c mice were established by intracardiac injection of luciferase-expressing 4T1luc mouse breast carcinoma cells. Mice with metastatic lesions received single intravenous (i.v.) injection of well-tolerated dose of scVEGF/(177)Lu (7.4 MBq/mouse) at day 8 after 4T1luc cell injection. Primary orthotopic breast tumors in immunodeficient mice were established by injecting luciferase-expressing MDA231luc human breast carcinoma cells into mammary fat pad. Tumor-bearing mice were treated with single injections of scVEGF/(177)Lu (7.4 MBq/mouse, i.v), or liposomal doxorubicin (Doxil, 1 mg doxorubicin per kg, i.v.), or with a combination of Doxil and scVEGF/(177)Lu given at the same doses, but two hours apart. Cold scVEGF-targeting conjugate was included in controls and in Doxil alone group. The effects of treatments were defined by bioluminescent imaging (BLI), computed tomography (CT), computed microtomography (microCT), measurements of primary tumor growth, and immunohistochemical analysis. RESULTS: In metastatic model, adjuvant treatment with scVEGF/(177)Lu decreased overall metastatic burden and improved survival. In orthotopic primary tumor model, a combination of Doxil and scVEGF/(177)Lu was more efficient in tumor growth inhibition than each treatment alone. scVEGF/(177)Lu treatment decreased immunostaining for VEGFR-1, VEGFR-2, and pro-tumorigenic M2-type macrophage marker CD206. CONCLUSIONS: Selective targeting of VEGFR with well-tolerated doses of scVEGF/(177)Lu is effective in metastatic and primary breast cancer models and can be combined with chemotherapy. As high level of VEGFR expression is a common feature in a variety of cancers, targeted delivery of (177)Lu for specific receptor-mediated uptake warrants further exploration

New Pulsars from an Arecibo Drift Scan Search

We report the discovery of pulsars J0030+0451, J0711+0931, and J1313+0931 that were found in a search of 470 square degrees at 430 MHz using the 305m Arecibo telescope. The search has an estimated sensitivity for long period, low dispersion measure, low zenith angle, and high Galactic latitude pulsars of ~1 mJy, comparable to previous Arecibo searches. Spin and astrometric parameters for the three pulsars are presented along with polarimetry at 430 MHz. PSR J0030+0451, a nearby pulsar with a period of 4.8 ms, belongs to the less common category of isolated millisecond pulsars. We have measured significant polarization in PSR J0030+0451 over more than 50% of the period, and use these data for a detailed discussion of its magnetospheric geometry. Scintillation observations of PSR J0030+0451 provide an estimate of the plasma turbulence level along the line of sight through the local interstellar medium.Comment: 21 pages, 4 figures, Accepted for Publication in Ap

Using Pulsars to Detect Massive Black Hole Binaries via Gravitational Radiation: Sagittarius A* and Nearby Galaxies

Pulsar timing measurements can be used to detect gravitational radiation from massive black hole binaries. The ~106d quasi-periodic flux variations in Sagittarius A* at radio wavelengths reported by Zhao, Bower, & Goss (2001) may be due to binarity of the massive black hole that is presumed to be responsible for the radio emission. A 106d equal-mass binary black hole is unlikely based on its short inspiral lifetime and other arguments. Nevertheless the reported quasi-periodicity has led us to consider whether the long-wavelength gravitational waves from a conjectured binary might be detected in present or future precision timing of millisecond pulsars. While present timing cannot reach the level expected for an equal-mass binary, we estimate that future efforts could. This inquiry has led us to further consider the detection of binarity in the massive black holes now being found in nearby galaxies. For orbital periods of ~2000d where the pulsar timing measurements are most precise, we place upper limits on the mass ratio of binaries as small as 0.06.Comment: 7 pages, 2 eps figures, accepted for publication in Ap